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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergic inflammation manifests as one of a number of diseases, including asthma, dermatitis, food allergy, vernal keratoconjunctivitis, and systemic anaphylaxis. Together these diseases affect nearly 25% of the Western world and are a leading health-care problem. The diseases are often biphasic, with an early phase driven primarily by mast cell degranulation and a late phase characterized by leukocyte recruitment. While chemokines are well known to be critical for leukocyte recruitment, their importance in early-phase reactions is poorly defined. We show here that administration of a single oral dose of a high affinity and highly selective CCR3 antagonist ablates both the early and late phase reactions in a mouse model of allergic conjunctivitis. A direct analysis of mast cells in the conjunctiva demonstrates that antagonism of the CCR3 receptor stabilizes the mast cell in vivo, thereby leading to the impaired early phase reaction. The late phase reaction is also strongly inhibited as characterized by both reduced eosinophilia and neutrophilia. These results constitute the first direct evidence that antagonism of CCR3 has clear potential for the treatment of allergic diseases.
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PMID:A specific CCR3 chemokine receptor antagonist inhibits both early and late phase allergic inflammation in the conjunctiva. 1646 99

Early nutritional events have the potential to affect health outcomes in later life including the development of allergy. Food allergy is usually the first manifestation of allergy. Breast-feeding has been associated with a protective effect against the development of allergy, but the evidence is contradictory and the mechanisms involved are not clear. We hypothesize that milk cytokines, such as transforming growth factor beta (TGF-beta), play a role in regulating immune responses to dietary antigens. Using a rat pup model of gastrostomy feeding, the immune response profile, at weaning and post-weaning, of allergy-prone Brown Norway rats fed formula supplementation with TGF-beta was assessed. We show that feeding formula to allergy-prone rat pups results in increased total IgE immunoglobulin, beta-lactoglobulin (BLG) IgG1 antibody, and mucosal mast cell activation, as measured by serum rat mast cell protease II (RMCPII) levels in the gut. Supplementation of formula with physiological levels of TGF-beta down-regulated the BLG IgG1 response as well as total IgE and mucosal mast cell activation. Supplementation of formula also resulted in an increase in Th1 cytokines, interleukin (IL)-18, IL-12p40, IL-12p35, and interferon gamma (IFN-gamma) and an increase in IL-10. In conclusion, TGF-beta supplementation of formula moved the immune response profile of allergy prone (Th2 type) rat pups toward a Th1 profile in the suckling period. Importantly, this immune profile persisted after weaning when TGF-beta was no longer present in the diet.
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PMID:Effects of transforming growth factor-beta and formula feeding on systemic immune responses to dietary beta-lactoglobulin in allergy-prone rats. 1662 76

Individuals with food allergy often present with uritcaria and atopic dermatitis. Indeed, susceptibility to food allergy may predispose to the development of these cutaneous allergic disorders. Recently, we developed a model of food allergy, whereby oral consumption of food [pea Pisum sativum L.; expressing alpha-amylase inhibitor-1 (alphaAI) from the common bean Phaseolus vulgaris L. cv Tendergreen (pea-alphaAI)] promotes a T helper cell type 2 (Th2) inflammatory response and predisposes to cutaneous allergic reactions following subsequent food allergen (alphaAI) exposure. To delineate the kinetics of food allergen-induced cutaneous reactions and examine the inflammatory mechanisms involved in this allergic reaction, we used interleukin (IL)-13-, IL-4 receptor alpha-, and eotaxin-1-deficient mice and performed serum transfer and CD4+ T cell depletion studies. We demonstrate that consumption of pea-alphaAI promotes an alphaAI-specific immunoglobulin G1 (IgG1) and IgE antibody response. Furthermore, we show that subsequent food allergen (alphaAI) challenge in the skin induced an early (3 h)- and late-phase (24 h) cutaneous allergic reaction. The early-phase response was associated with mast cell degranulation and the presence of Ig, whereas the late-phase response was characterized by a lymphoid and eosinophilic infiltrate, which was critically regulated by CD4+ T cells, IL-13, and eotaxin-1. Collectively, these studies demonstrate that food allergy can predispose to cutaneous inflammatory reactions, and these processes are critically regulated by Th2 immune factors.
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PMID:Mechanistic analysis of experimental food allergen-induced cutaneous reactions. 1686 16

The mechanism of food allergy remains unclear. The absorption of intact protein Ag into the intestinal tissue is a prerequisite in the development of intestinal sensitization. Previous studies indicate that thermal stress compromises the intestinal barrier function. Mice were concurrently exposed to thermal stress and oral Ag. Intestinal sensitivity, levels of serum-specific IgE, IL-4 and INF-gamma were assessed. Intestinal dendritic cell, Th1 and Th2 functions were determined. The mice that were treated with thermal stress and oral Ag showed high levels of serum Ag-specific IgE, intestinal mast cell activation in response to oral Ag challenge, suppression of IL-12 expression in the intestinal dendritic cells, inhibition of T-bet expression and Th1 function and marked increases in (GATA)3 expression and Th2 function. Mice exposed to thermal stress alone or oral Ag alone did not show any signs of the intestinal sensitization. Pretreatment with IL-12 inhibited the intestinal sensitization induced by the concurrent exposure to thermal stress and Ag gavage. We conclude that although Ag absorption is essential, Ag absorption alone is insufficient; other accessory factors that can disturb the local immune homeostasis are also required for the induction of intestinal sensitization. The present study illustrates that concurrent exposure to thermal stress and oral Ag can prove to be a factor in the induction of intestinal sensitization by a mechanism of regulating IL-12 expression.
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PMID:Concurrent exposure to thermal stress and oral Ag induces intestinal sensitization in the mouse by a mechanism of regulation of IL-12 expression. 1694 86

Although many authors have considered a direct interaction between allergic reactions and behavioral changes, supporting evidence has been elusive. In this series of studies we show that after oral or nasal ovalbumin (OVA) challenge, allergic mice present increased Fos expression in the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA). Mice with food allergy display higher levels of anxiety and increased serum corticosterone levels, and allergy-activated neurons express corticotropin-releasing factor (CRF) in the PVN and CeA. OVA-allergic mice develop aversion to an antigen-containing solution, and also avoid a dark compartment previously associated with nebulized OVA. Results on brain Fos expression and behavioral data seem compatible with adaptive responses. Removal of IgE by either antibody depletion or the development of oral tolerance precluded all responses analyzed here. C-sensitive fiber destruction by neonatal capsaicin inhibited the activation in the PVN, but not in the CeA, and decreased the magnitude of food aversion. Cromolyn, a mast cell stabilizer, completely blocked Fos expression in the PVN and CeA, and precluded the development of aversion to the dark compartment associated with nebulized OVA. Employing mice that do not develop an important inflammatory infiltrate following nasal OVA challenge, we found that inflammatory cells are not required at the site of challenge in order to trigger neural or behavioral correlates of murine experimental asthma. Altogether, we have built a solid foundation for understanding neuroimmune interactions during allergic responses that may contribute to the comprehension of psychological disorders associated with allergy.
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PMID:Neural correlates of IgE-mediated allergy. 1719 60

Childhood cow's milk allergy is a diagnosis encompassing various syndromes. Antigen-immunoglobulin E (IgE) antibody interaction is classically involved in mast cell degranulation in IgE-mediated food allergy, while non-IgE mediated cow's milk allergy is mostly mediated by cellular mechanisms. The diagnosis of cow's milk allergy largely relies on a good knowledge of the clinical expression of the disease. In this educational review series, we describe three cases of cow's milk allergy, first a 7-yr-old girl with persisting IgE-mediated cow's milk allergy, second a 8-month-old boy with cow's milk induced flares of atopic dermatitis, and third a 6-yr-old boy with sheep and goat milk allergy, in the absence of cow's milk allergy. The cases are discussed and summarized with more general recommendations for the clinical management of cow's milk allergy.
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PMID:The spectrum of cow's milk allergy. 1839 12

A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.
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PMID:CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice. 1791 45

Previous mouse and clinical studies demonstrate a link between Th2 intestinal inflammation and induction of the effector phase of food allergy. However, the mechanism by which sensitization and mast cell responses occurs is largely unknown. We demonstrate that interleukin (IL)-9 has an important role in this process. IL-9-deficient mice fail to develop experimental oral antigen-induced intestinal anaphylaxis, and intestinal IL-9 overexpression induces an intestinal anaphylaxis phenotype (intestinal mastocytosis, intestinal permeability, and intravascular leakage). In addition, intestinal IL-9 overexpression predisposes to oral antigen sensitization, which requires mast cells and increased intestinal permeability. These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9-mediated mast cell responses have an important role in food allergy.
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PMID:IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. 1837 96

Various inflammatory mediators released from antigen-activated mast cells are considered to play a key role in the pathogenesis of food allergy. The aim of the present study was to determine the mechanisms underlying the antigen-induced anaphylactic responses in the rat colons. Wistar rats were sensitized by intraperitoneal injection of ovalbumin (OVA). The contractilities of isolated proximal colons of the sensitized rats were studied in the organ bath. OVA challenges of sensitized tissues induced prolonged contractile responses. The antigen-induced contractions were greatly reduced by mast cell stabilizer doxantrazole (10 microM). However, the contractions were resistant to histamine H1 receptor antagonist and prostaglandin D2 receptor antagonist. In contrast, non-selective cyclooxygenase (COX) inhibitor indomethacin (1 microM) significantly reduced the contractions by 61.0%. Furthermore, selective COX-1 inhibitor FR122047 (10 microM) as well as selective COX-2 inhibitor NS-398 (10 microM) significantly inhibited the contractions by 50.1% and 50.3%, respectively. Nevertheless, the transcript levels of COX-2 as well as COX-1 were not upregulated by OVA in the proximal colons of the sensitized rats. The present results indicate that de novo arachidonic acid metabolites synthesis by constitutive COX-1 as well as constitutive COX-2 within mast cells contribute to the altered smooth muscle contractilities in the colons under the anaphylactic condition.
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PMID:The pathophysiological roles of COX-1 and COX-2 in the intestinal smooth muscle contractility under the anaphylactic condition. 1848 May 53

Gender differences in the development and prevalence of human diseases have long been recognized. Immense interest grows in the understanding of the role of sex hormones in the homeostasis of immunity. Asthma predominates in boys before puberty and this gender preference reverses after puberty and in adulthood, when adult women tend to have a more severe disease, often recalcitrant to treatment. Atopic eczema in preschool children shows insignificant gender difference or male preponderance in different studies, with more adult females suffering from atopic eczema. The limited data on the prevalence of immediate hypersensitivity to hymenoptera venom show controversial results. Discrepancy exists regarding the gender difference in food allergy, with females reporting significantly more allergic reactions in questionnaire studies. In general, adverse reactions to nonionic iodinated radiocontrast media are more commonly observed in females. The course of allergic diseases varies unpredictably during pregnancy, whereas hormone replacement therapy in postmenopausal women usually has a favorable influence on the course of asthma. Experiments in rodents confirm an effect of estrogens on mast cell activation and allergic sensitization, while progesterone is shown to suppress histamine release but potentiate IgE induction. Dehydroepiandrosterone may antagonize the production of Th2 cytokines but the effect of testosterone and the other androgens remains less defined. Actual data from human studies are lacking.
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PMID:Gender difference, sex hormones, and immediate type hypersensitivity reactions. 1892 78


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